Effective Prognostic Model for Therapy Response Prediction in Acute Myeloid Leukemia Patients

SIMPLE SUMMARY: Acute myeloid leukemia (AML) is a hematopoietic disorder characterized by the malignant transformation and abnormal proliferation of bone marrow-derived myeloid progenitors. To select the optimal treatment regimens and predict the therapy response in AML patients, stratification into risk groups based mostly on genetic factors is carried out. Despite this contemporary approach, tumor cell resistance to chemotherapeutic drugs represents one of the main obstacles for improving survival outcomes in AML. In the present study, a new prognostic scale for risk stratification of AML patients based on the drug responsiveness of tumor cells detected in vitro as well as MDR1 mRNA/P-glycoprotein expression, tumor origin (primary or secondary), cytogenetic abnormalities, and aberrant immunophenotype was developed. Using correlation, ROC, and Cox regression analyses, we demonstrated that the risk stratification of AML patients in accordance with the developed prognostic scale correlates well with the response to therapy and represents an independent predictive factor for the overall survival of patients with newly diagnosed AML. ABSTRACT: Acute myeloid leukemia (AML) is a hematopoietic disorder characterized by the malignant transformation of bone marrow-derived myeloid progenitor cells with extremely short survival. To select the optimal treatment options and predict the response to therapy, the stratification of AML patients into risk groups based on genetic factors along with clinical characteristics is carried out. Despite this thorough approach, the therapy response and disease outcome for a particular patient with AML depends on several patient- and tumor-associated factors. Among these, tumor cell resistance to chemotherapeutic agents represents one of the main obstacles for improving survival outcomes in AML patients. In our study, a new prognostic scale for the risk stratification of AML patients based on the detection of the sensitivity or resistance of tumor cells to chemotherapeutic drugs in vitro as well as MDR1 mRNA/P-glycoprotein expression, tumor origin (primary or secondary), cytogenetic abnormalities, and aberrant immunophenotype was developed. This study included 53 patients diagnosed with AML. Patients who received intensive or non-intensive induction therapy were analyzed separately. Using correlation, ROC, and Cox regression analyses, we show that the risk stratification of AML patients in accordance with the developed prognostic scale correlates well with the response to therapy and represents an independent predictive factor for the overall survival of patients with newly diagnosed AML.